Potent immune responses and in vitro pro-inflammatory cytokine suppression by a novel adenovirus vaccine vector based on rare human serotype 28

Christoph A. Kahl, Jessica Bonnell, Suja Hiriyanna, Megan Fultz, Cassandra Nyberg-Hoffman, Ping Chen, C. Richter King, Jason G.D. Gall

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Adenovirus vaccine vectors derived from rare human serotypes have been shown to be less potent than serotype 5 (Ad5) at inducing immune responses to encoded antigens. To identify highly immunogenic adenovirus vectors, we assessed pro-inflammatory cytokine expression, binding to the CD46 receptor, and immunogenicity. Species D adenoviruses uniquely suppressed pro-inflammatory cytokines and induced high levels of type I interferon. Thus, it was unexpected that a vector derived from a representative serotype, Ad28, induced significantly higher transgene-specific T cell responses than an Ad35 vector. Prime-boost regimens with Ad28, Ad35, Ad14, or Ad5 significantly boosted T cell and antibody responses. The seroprevalence of Ad28 was confirmed to be <10% in the United States. Together, this shows that a rare human serotype-based vector can elicit strong immune responses, which was not predicted by . in vitro results.

Original languageEnglish (US)
Pages (from-to)5691-5702
Number of pages12
JournalVaccine
Volume28
Issue number35
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • Adenovirus
  • Human vaccine
  • Seroprevalence
  • Vector

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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